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Biomedical subjects

G A Storch

Publications and source records attributed to G A Storch.

At least 55 records · Page 3Linked to original sources

Epstein-Barr virus DNA in peripheral blood leukocytes of patients with posttransplant lymphoproliferative disease.

We tested the hypotheses that Epstein-Barr virus (EBV) DNA levels in peripheral blood leukocytes (PBL) of transplant recipients with posttransplant lymphoproliferative disease (PTLD) (1) exceed those of patients without PTLD, (2) rise with or before clinical detection of the disease, and (3) fall with effective therapy. Using the polymerase chain reaction (PCR) and an endpoint dilution technique, we compared EBV DNA levels in sequential specimens from 5 patients with PTLD, 16 solid organ transplant recipients without PTLD, and 5 young adults with primary infectious mononucleosis (IM), and in single specimens from 21 healthy seropositive subjects. EBV DNA levels in the first two groups rose with induction of immunosuppression despite prophylactic acyclovir. Markedly elevated levels of EBV DNA were seen in 4 of 5 patients with PTLD at or before clinical diagnosis. The peak levels in these patients exceeded those of transplant recipients without PTLD (P = 0.02) and healthy adults with IM (P = 0.02). EBV DNA levels fell dramatically with effective therapy. Four of 21 healthy seropositive subjects demonstrated low levels of EBV DNA, similar to levels seen late in the course of patients with IM. We conclude that a semiquantitative PCR assay for EBV DNA in PBL can assist in the detection of PTLD and in monitoring the effect of therapy.

Adolescent↗

Direct quantitative comparison of shell vial and conventional culture for detection of CMV viremia.

BACKGROUND: Centrifugation shell vial (SV) and conventional tube culture (TC) are the most common methods for detecting cytomegalovirus (CMV) viremia. Studies have indicated that SV is more sensitive than TC but at least one report suggested that TC was more sensitive. Because CMV in the blood is primarily associated with infected leukocytes, the number of leukocytes inoculated into the different culture systems could affect the sensitivities of the two systems. OBJECTIVES: To compare the sensitivities of SV and TC for detection of CMV viremia by inoculating equal numbers of leukocytes into paired SV cultures and TC cultures. STUDY DESIGN: Leukocytes from transplant recipients were isolated and counted. Equal numbers of leukocytes were then inoculated into each of two MRC-5 SV and into each of two MRC-5 TC. SV was considered positive when either one or both vials were positive, and TC was considered positive when either one or both tubes showed evidence of CMV cytopathic effect (CPE). RESULTS: From a total of 434 specimens tested, 85 (19.6%) were positive by SV or TC. CMV was detected by SV in 75 (88%) of the positive specimens, compared to TC which was positive in 40 (47%) of the positive specimens. CONCLUSIONS: When equal numbers of leukocytes were inoculated into each system, SV had significantly greater sensitivity than TC for detecting CMV viremia. However, a small number of episodes of viremia were detected only by TC. Therefore, both methods should be used for maximum sensitivity.

Journal Article↗

Expanded spectrum of herpes simplex encephalitis in childhood.

We designed a polymerase chain reaction method to detect herpes simplex virus (HSV) DNA in spinal fluid from patients with encephalitis. The polymerase chain reaction amplified a 211 base-pair segment of the HSV DNA polymerase gene. Applying this method, we diagnosed HSV type 1 infection in three young children, aged 7 to 13 months, who had atypical forms of the illness. On the basis of magnetic resonance imaging, their disease was diffuse or multifocal in two cases and, in all three, lacked the temporal lobe involvement considered characteristic of HSV encephalitis beyond the neonatal period. Most of the diffuse or multifocal abnormalities detected by magnetic resonance imaging were not apparent by computed tomography. Restriction enzyme analysis of the polymerase chain reaction products from all three patients indicated that their disease was caused by HSV type 1. We conclude that in preschool-age children beyond the neonatal period, the spectrum of HSV encephalitis includes multifocal or diffuse involvement of the brain, which may be detected most efficiently by magnetic resonance imaging. The polymerase chain reaction method has the potential for providing an early diagnosis, but further studies are required to define the sensitivity and specificity of the polymerase chain reaction before it can be used for routine clinical decision making.

Antibodies, Viral↗

Herpes simplex virus type 2 meningitis in the absence of genital lesions: improved recognition with use of the polymerase chain reaction.

Herpes simplex virus type 2 (HSV-2) is known to cause aseptic meningitis, which can be recurrent. The diagnosis of HSV-2 infection is suggested when meningitis occurs simultaneously with genital lesions but may be obscure if genital lesions are not present or are not appreciated. Viral culture of the CSF is sometimes positive, but it may also be negative, especially in cases of recurrent disease. We report three cases of HSV meningitis in young women who did not have a history of genital herpetic lesions and for whom genital lesions were not noted on presentation. With use of the polymerase chain reaction (PCR), HSV DNA was detected in CSF from all three patients. The diagnosis of HSV meningitis was further confirmed by a positive culture of CSF in one patient's case and by demonstration of intrathecal synthesis of HSV antibodies in a second patient's case. The use of PCR can improve the recognition of HSV meningitis in adults presenting with aseptic meningitis, even in the absence of herpetic lesions.

Adult↗

Quantitative analysis of cytomegalovirus viremia in lung transplant recipients.

A quantitative culture method was used to test serial blood specimens from 28 lung transplant recipients at risk of cytomegalovirus (CMV) infection (donor [D] or recipient [R] seropositive for CMV). Viremia occurred in 26 (93%) of 28 patients. Highest levels were seen when the donor was seropositive. The median of individual maximum levels was 2.13 infectious centers (ICs/10(5) leukocytes for D+/R- patients (interquartile range [iqr], 0.12-21.77), 1.01 for D+/R+ (iqr, 0.3-2.32), and 0.10 for D-/R+ (iqr, 0.07-0.36; P = .030, Kruskal-Wallis test). Higher levels were seen in patients with biopsy-proven CMV pneumonitis compared with those with negative biopsies (mean, 0.24 [SD 0.51] ICs/10(5) leukocytes vs. 0.01 [SD 0.03]; P = .039, Wilcoxon test) and with symptomatic CMV episodes compared with asymptomatic episodes (median, 0.34 ICs/10(5) [iqr, 0.11-0.61] vs. 0.08 ICs/10(5) [iqr, 0.03-0.13]; P = .045, Wilcoxon test). Further studies are required to determine whether quantification of CMV viremia by this method will be of practical value in the recognition of significant CMV infection in lung transplant recipients.

Antigens, Viral↗

Level of cytomegalovirus (CMV) DNA in cerebrospinal fluid of subjects with AIDS and CMV infection of the central nervous system.

The objective of this study was to correlate cytomegalovirus (CMV) DNA levels in the cerebrospinal fluid (CSF) of subjects with AIDS with clinical and pathologic findings attributable to CMV infection of the central nervous system (CNS). CMV polymerase chain reaction (PCR) was done on serial dilutions of CSF samples from 24 AIDS patients with autopsy-proven CNS disorders. CMV DNA was detected in CSF from 12 of 13 subjects with evidence of CMV infection of the brain or spinal cord but in none of 11 subjects without autopsy evidence of CMV CNS infection. Subjects whose CSF contained > 10(3) CMV DNA molecules/8 microL of CSF had severe CMV CNS disease (e.g., ventriculoencephalitis). PCR appears to be more useful than clinical and neuroradiologic findings for documenting CMV infection of the CNS in patients with AIDS. Quantitation of CMV DNA in CSF shows promise for evaluation of the extent of involvement.

AIDS-Related Opportunistic Infections↗

Comparison of automated Difco ESP blood culture system with biphasic BBL Septi-Chek system for detection of bloodstream infections in pediatric patients.

We compared the Difco ESP 384 blood culture system with the pediatric Septi-Chek system for the detection of bloodstream infections in pediatric patients. A total of 10,762 blood culture sets included an ESP aerobic bottle and a Septi-Chek bottle. From these cultures, a total of 278 organisms classified as probable pathogens were isolated, including 237 from ESP bottles and 221 from Septi-Chek bottles. This difference was not statistically significant. More organisms classified as possible contaminants were also isolated from ESP bottles (for ESP, 480 bottles; for Septi-Chek, 418 bottles; P < 0.01). The time to detection was shorter for probable pathogens isolated from ESP bottles (median times for organisms isolated from both systems: ESP, 14.0 h; Septi-Chek, 34.5 h; P < 0.001). The proportions of all probable pathogens detected by 24 and 48 h after inoculation were 78 and 96%, respectively, for ESP compared with 31 and 74%, respectively, for Septi-Chek. The time to final identification was also shorter for organisms grown in ESP bottles (median times for organisms isolated from both systems: ESP, 48.8 h; Septi-Chek, 58.5 h; P < or = 0.001). A subset of 4,442 cultures also included an ESP anaerobic bottle in addition to an ESP aerobic bottle and a Septi-Chek bottle. There were no significant differences in the recovery of probable pathogens by any of the possible two bottle combinations, but five anaerobic pathogens were recovered only in the anaerobic bottle. We conclude that the ESP 384 is an excellent system for culturing pediatric blood samples and that it provides for the very rapid detection of bloodstream pathogens.

Adolescent↗

Detection of Epstein-Barr virus DNA in cerebrospinal fluid for diagnosis of AIDS-related central nervous system lymphoma.

The diagnostic utility of Epstein-Barr virus (EBV) DNA detection in cerebrospinal fluid for the diagnosis of central nervous system lymphoma was evaluated with two different PCR assays to test a collection of cerebrospinal fluid samples from 24 AIDS patients with central nervous system disorders. A PCR assay amplifying a fragment from the BamHI-W region had the highest clinical and analytic sensitivity. The BamHI-W PCR assay detected EBV DNA in cerebrospinal fluid from 83% (5 of 6) of patients with pathologically proven primary central nervous system lymphoma and 7% (1 of 16) of controls with autopsy-proven nonlymphomatous central nervous system disorders. EBV DNA was also detected in one patient with autopsy-proven systemic lymphoma involving the central nervous system and one patient with probable primary central nervous system lymphoma. EBV DNA was detected consistently when central nervous system lymphoma involved meningeal surfaces. PCR for EBV in cerebrospinal fluid appears to be useful for diagnosis of AIDS-related central nervous system lymphoma, but additional studies are required to better define the sensitivity of the assay and to understand the significance of a positive test in the absence of lymphoma.

Central Nervous System Neoplasms↗

Vaccinia keratouveitis manifesting as a masquerade syndrome.

A patient who used contact lenses and had a history of blunt trauma developed vaccinia keratouveitis after accidental ocular autoinoculation from a recent vaccination site. Corneal and conjunctival cultures were taken for bacteria, fungi, Acanthamoeba, and viruses. Viral-like cytopathic effects became evident in tissue culture within three days. Immunofluorescence studies were negative for varicella-zoster virus, herpes simplex virus, adenovirus, measles, mumps, parainfluenza, and influenza. Pox viral particles were identified in the infected tissue cultures by electron microscopy. The Hind III restriction endonuclease profile of the viral DNA isolate was similar to the Lister strain of vaccinia virus. Ocular vaccinia may manifest as a masquerade syndrome and may mimic signs of herpes simplex virus, varicella-zoster virus, and Acanthamoeba infection. Although vaccination with vaccinia is currently limited to a few populations throughout the world, vaccinia must still be considered in the differential diagnosis of infectious keratouveitis.

Adult↗

Resistance to penicillin and non-beta-lactam antibiotics of Streptococcus pneumoniae at a children's hospital.

During a 12-month period we tested all isolates of Streptococcus pneumoniae recovered from patients at St. Louis Children's Hospital for resistance to penicillin and other antibiotics. Twenty-seven (20%) of 136 had relative penicillin resistance (minimum inhibitory concentration 0.1 to 1.0 microgram/ml) and 8 (6%) were fully resistant (minimum inhibitory concentration > or = 2.0 micrograms/ml). Sixteen percent from blood and cerebrospinal fluid were resistant, compared with 30% from other body sites. The resistant isolates were of diverse serotypes and included 38% intermediate and 6% resistant to cefotaxime, 40% resistant to trimethoprim-sulfamethoxazole and 20% resistant to erythromycin. Patients with resistant isolates were more likely to have taken antibiotics of the aminopenicillin class and to be of the white race. We conclude that penicillin-resistant pneumococci, including some with resistance to third generation cephalosporins and some with multidrug resistance to non-beta-lactam antibiotics, are widespread in the St. Louis area. The presence of these stains requires reconsideration of current approaches to the antibiotic therapy of a variety of infectious diseases in which pneumococci play a prominent role.

Drug Resistance, Microbial↗

Comparison of heparin and EDTA transport tubes for detection of cytomegalovirus in leukocytes by shell vial assay, pp65 antigenemia assay, and PCR.

The anticoagulants heparin and EDTA were compared for inhibitory effects on the detection of cytomegalovirus from washed leukocytes in specimen transport tubes. Evaluation was made by the centrifugation/shell vial culture technique, the pp65 antigenemia assay, and PCR. For each assay, the results with heparin and EDTA were equivalent.

Antigens, Viral↗

Comparison of PCR and pp65 antigenemia assay with quantitative shell vial culture for detection of cytomegalovirus in blood leukocytes from solid-organ transplant recipients.

This study compared PCR and an assay for cytomegalovirus (CMV) pp65 antigenemia (CMV-vue; INCSTAR Corp.) with a quantitative shell vial culture (QSVC) technique for the detection of CMV in serial blood specimens from 46 solid-organ transplant recipients. In a comparison based on 535 specimens tested by PCR and QSVC, CMV was detected by PCR in 41 and by QSVC in 37 of 43 recipients at risk of CMV infection. The mean number of days after transplantation of initial detection of CMV was 29.9 for PCR and 34.0 for QSVC (P = 0.01). The antigenemia assay was performed on 395 specimens, including 304 of those also tested by PCR. In these specimens, CMV was detected by the antigenemia assay, QSVC, and PCR in 30, 32, and 35 (respectively) of 38 patients at risk, with no statistically significant difference in the time to detection. Each of the assays detected CMV in similar proportions of patients with and without clinically significant CMV infection. PCR stayed positive longer after transplantation than the other assays but frequently returned to negative when more than 6 months had elapsed after transplantation. The antigenemia assay and PCR stayed positive longer after institution of antiviral therapy than QSVC. PCR can provide highly sensitive detection of CMV viremia, but a PCR assay for CMV is not yet available in kit form. The pp65 antigenemia assay and shell vial culture are quantifiable and comparable in sensitivity. Either is recommended for rapid detection of CMV in blood specimens from solid-organ transplant recipients.

Antigens, Viral↗

Enteroviral meningitis in infancy: potential role for polymerase chain reaction in patient management.

STUDY OBJECTIVE: To evaluate the performance characteristics and potential clinical utility of a polymerase chain reaction (PCR) assay for enteroviral RNA in comparison to viral culture in infants under 3 months of age with meningitis. SPECIMENS AND TESTING: Specimens were obtained from a collection of cerebrospinal fluid specimens from infants under 3 months of age (excluding those in the neonatal intensive care unit) undergoing lumbar puncture at St. Louis Children's Hospital during a 12-month period. Those tested by PCR included all 27 with pleocytosis, 8 others from infants without pleocytosis but from whom an enterovirus was cultured, and 10 from infants who did not have pleocytosis and had a negative viral culture of cerebrospinal fluid. Viral cultures were performed at the discretion of physicians caring for individual patients. RESULTS: PCR was positive for enteroviral RNA on cerebrospinal fluid (CSF) specimens from 11 of 12 patients with definite or probable enteroviral meningitis, as well as on 6 of 13 with possible enteroviral meningitis, and was negative on all 10 with absence of pleocytosis and negative enteroviral cultures. CSF viral cultures were negative in 6 of the patients in whom PCR was positive. Viral cultures had minimal impact on patient management. In contrast, under study assumptions, PCR could have saved an average of 1.2 days of hospitalization per patient in the 27 patients with CSF pleocytosis. CONCLUSIONS: Enterovirus PCR performed on CSF is a sensitive and specific method for the diagnosis of enteroviral meningitis. This method has the potential for improving the accuracy of diagnosis in young infants and for saving costs by allowing earlier diagnosis and discharge from the hospital when clinically appropriate.

Cerebrospinal Fluid↗

Failure of high-dose oral acyclovir with or without immune globulin to prevent primary cytomegalovirus disease in recipients of solid organ transplants.

PURPOSE: To assess the efficacy of acyclovir and intravenous immune globulin (IVIG) for cytomegalovirus (CMV) prophylaxis in high-risk recipients of solid organ transplants. PATIENTS AND METHODS: We randomized 21 CMV-seronegative organ transplant recipients with seropositive donors (D+R-) to receive oral acyclovir, 800 mg four times daily, or, in addition to acyclovir, IVIG, 300 mg/kg, every 2 weeks for six doses. Patients were followed closely for the development of CMV infection and disease. RESULTS: All but one prophylactically treated patient (95%) developed CMV infection. Fifteen of 21 patients (71%) who received prophylaxis fulfilled criteria for CMV disease. Disease onset was delayed in those who received IVIG, but this did not reach statistical significance. Ganciclovir was used for treatment in 15 of the 21 patients (71%). CONCLUSIONS: Acyclovir, with or without IVIG, did not prevent primary CMV infection or disease in D+R- solid organ transplant recipients at our institution. Moreover, most patients were treated with ganciclovir despite the use of prophylaxis. Given the ready availability of ganciclovir to treat CMV disease, we recommend a reappraisal of the role of CMV prophylaxis by these means in the solid organ transplant population.

Acyclovir↗

Symptomatic cytomegalovirus infection in renal transplant recipients given either Minnesota antilymphoblast globulin (MALG) or OKT3 for rejection prophylaxis.

To compare the impact of using Minnesota antilymphoblast globulin (MALG) versus the monoclonal antibody, OKT3, on the development of symptomatic cytomegalovirus (CMV) infection, we reviewed a cohort of 130 cadaveric renal transplant recipients enrolled in a prospective comparison of MALG versus OKT3 for rejection prophylaxis. Among the 112 patients at risk for CMV, prophylactic MALG was associated with an increased risk of symptomatic infection (relative hazard [rh] = 3.31; 95% confidence interval CI], 1.50 to 7.30; P = 0.003). Transplantation of kidneys from CMV-seropositive donors into CMV-seronegative recipients (rh = 5.22; 95% CI, 2.34 to 11.63; P = 0.00004), first transplantation (rh = 4.76; 95% CI, 1.06 to 21.3; P = 0.039), and acute rejection therapy (rh = 2.03; 95% CI, 0.98 to 4.21; P = 0.055) were also associated with an increased risk. Prophylactic MALG followed by treatment with any agent for acute rejection was strongly correlated with symptomatic CMV infection (rh = 4.46; 95% CI, 3.71 to 5.21; P = 0.00006). Symptomatic CMV infection was not only more frequent, but more severe in recipients of prophylactic MALG, and more MALG recipients were treated with ganciclovir. There was no difference in rejection rate for the two rejection prophylaxis regimens (P = 0.625). Prophylactic OKT3 results in less risk of symptomatic CMV infection than prophylactic MALG in cadaveric renal transplant recipients who are seropositive for CMV or whose donors are seropositive for CMV.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Antigenic and nucleic acid analysis of nosocomial isolates of respiratory syncytial virus.

Monoclonal antibodies and ribonuclease protection were used to analyze antigenic and genomic diversity among 42 isolates of group A respiratory syncytial virus (RSV) from studies of nosocomial RSV carried out at the University of Rochester during the 1974-1975 and 1975-1976 RSV seasons. Three distinct subgroups or lineages and a total of 12 viral variants were present. Against this background of diversity, an outbreak was recognized that included 13 indistinguishable isolates occurring during a 2-week period. This outbreak accounted for 6 of the 8 infants with nosocomial infection. In contrast to the limited diversity of the nosocomial isolates, isolates from the 10 infants with community-acquired infection included 8 variants. Like those from community outbreaks of RSV, isolates of RSV from hospitalized patients are virologically heterogeneous. However, discrete outbreaks associated with transmission of a single strain can occur.

Acute Disease↗

Quantitative cultures of the cell fraction and supernatant of bronchoalveolar lavage fluid for the diagnosis of cytomegalovirus pneumonitis in lung transplant recipients.

Results of quantitative shell vial cultures of cell and supernatant fractions of bronchoalveolar lavage (BAL) fluid from lung transplant recipients were compared with results of transbronchial lung biopsies. Cytomegalovirus (CMV) was present in both the cell and supernatant fractions, including 28 (80%) and 29 (83%), respectively, of 35 BAL samples with corresponding biopsies that showed evidence of CMV pneumonitis and 34 (15%) and 75 (33%), respectively, of 227 BAL samples with corresponding biopsies that did not. Cultures of unseparated BAL fluid had a similar yield to cultures of supernatant. Virus titers of cell fractions and supernatants from BAL samples with corresponding biopsies that were positive for CMV pneumonitis were higher than those from BALs with negative corresponding biopsies. Culture of the unseparated fluid is recommended for simplicity and to maximize detection of CMV. Quantitative results may help in the identification of CMV pneumonitis, but additional studies are needed before quantitative cultures can be recommended for routine use.

Bronchoalveolar Lavage Fluid↗